Hearing loss in the elderly, presbycusis, is the number one communicative disorder of the elderly. Classically, loss of sensory cells (hair cells) in the basal (high pitch) portion of the cochlear (inner ear of the peripheral auditory system) has contributed to presbycusis. Other more recent evidence points to age-related changes in the brain itself (central auditory system) as a cause of presbycusis. These two factors result in the two main perceptual difficulties: a high-pitch loss in sensitivity and a difficulty of understanding speech in background noise. During the previous funding period, significant age-related changes were observed in animals with age-related auditory temporal pathways, electron microscopy of midbrain synapses, cochlear inner and outer hair cell degeneration, and others. In the upcoming grant period, techniques of cellular neuroimaging will be applied in slice preparations of young and old animals to determine calcium regulatory changes with age in brain regions we previously demonstrated had age-related temporal processing deficits, as well as determining if manipulation of intracellular calcium concentration levels and stores will affect the processing of auditory temporal information. Close ties will exist with the Animal Behavior Project (acoustic startle response- Project 2), the Single-unit Physiology Project (midbrain, cochlear nucleus- Project 3), and the Human and Animal Evoked Potential Project (animal Wave I and IV- Project 5). These neurophysiological and behavioral projects will evaluate any age-related improvements in temporal processing in old CBA mice that may occur due to loading the inferior colliculus (IC) of young, adult mice with increased calcium regulators in the present project. In addition, HRP immunohistochemistry will continue to be performed in conjunction with the single-unit neurophysiological mapping experiments of Project 3. Specifically, inputs to the ventrolateral division of the central nucleus of IC will be compared to the decline inputs to dorsomedial IC that we have already discovered with age. Descending inputs to the central cochlear nucleus from higher centers of the brain will be examined to see if any age-related changes in connectivity occur. The results of these studies will be utilized to prepared for medical/surgical/technological interventions to increase the quality of life in our elderly population, especially in regard to sensory perception and brain functioning.